PHARMACOKINETICS OF ESOMEPRAZOLE IN ADOLESCENT PATIENTS AGED 12 TO 17 YEARS INCLUSIVE WITH SYMPTOMS OF GASTROESOPHAGEAL REFLUX DISEASE

Abstract

Aim: To determine the pharmacokinetics (PK) of esomeprazole after single and repeated oral doses in adolescent patients (age, 12-17 years inclusive) with gastroesophageal reflux disease (GERD) symptoms. Methods: In this single-center, randomized, open-label study (D961400094), 28 adolescents (13 girls) received esomeprazole 20-or 40-mg capsules once daily for 8 days. Blood samples were taken at 0, 0.5, 1, 1.5, 2, 3, 4 and 6 hours post dose on days 1 and 8. Normal-phase liquid chromatography and ultraviolet detection (limit of quantification, 0.025 μmol/L) were used to determine plasma esomeprazole concentrations. PK parameters were calculated by a noncompartmental approach using WINNONLIN software. Results: The PK parameters of these adolescents and published values (Physician's Desk Reference Electronic Library [pdrel.thomsonhc.com]) of adults with suspected or established GERD are shown below. Summary: Esomeprazole seems to have both dose-and time-dependent PK changes in these patients. A doubled dose results in more than a doubled overall exposure (AUC) and Cmax for both single and repeated doses. The T½ was also approximately 50% longer for the higher or repeated dose compared with the lower or single dose. The PK parameters in adolescents are generally comparable with those observed in adults. The few observed adverse events were of mild intensity. Conclusion: The PK profile of esomeprazole in adolescent patients with symptoms of GERD is similar to that in adults.Table